Effect of Rifaximin on Thrombocytopenia in Patients With HCV-Related Liver Cirrhosis

Overview

Cirrhosis is a common complication of chronic hepatitis C virus (HCV) infection in Egypt. Thrombocytopenia (TP) is the most common cytopenia in patients with cirrhosis and may be associated with variceal bleeding, rebleeding, morbidity, and mortality. Although TP has traditionally been attributed to portal hypertension and splenic sequestration, other mechanisms include impaired thrombopoietin activity, bone marrow suppression, and increased platelet destruction. Rifaximin is a poorly absorbed, broad-spectrum intestinal antimicrobial agent widely used in patients with cirrhosis, particularly for hepatic encephalopathy. Its minimal systemic absorption limits systemic adverse effects. Rifaximin may reduce intestinal bacterial overgrowth and bacterial translocation, thereby decreasing circulating endotoxin and proinflammatory cytokines that may contribute to haematological abnormalities in cirrhosis. Previous observations have suggested that intestinal decontamination with rifaximin may increase platelet counts in patients with cirrhosis and thrombocytopenia. This randomised controlled trial was designed to investigate whether rifaximin treatment could improve platelet count in patients with HCV-related liver cirrhosis and thrombocytopenia.

After approval by the Ethics Committee of the Faculty of Medicine, Fayoum University, patients were recruited from two tertiary university hospitals in Egypt. Written informed consent was obtained from all patients before enrolment. This was a double-blind, randomised controlled clinical trial that included 165 adults aged 18-75 years with HCV-related liver cirrhosis and thrombocytopenia who had previously received treatment for HCV and achieved a sustained virologic response. Cirrhosis was diagnosed based on clinical findings (splenomegaly, ascites, and/or esophageal varices), laboratory findings (hypoalbuminemia, hyperbilirubinemia, and/or prolonged prothrombin time), and imaging findings on abdominal ultrasonography, computed tomography, and/or magnetic resonance imaging, with liver biopsy considered when available. The severity of cirrhosis was assessed using the Child-Pugh classification. Thrombocytopenia was defined as a platelet count \<150,000/mm³ and classified as mild (\>75,000/mm³), moderate (50,000-75,000/mm³), or severe (\<50,000/mm³). Anaemia was defined as haemoglobin \<13.5 g/dL in men and \<11.5 g/dL in women, and leukopenia as a white blood cell count \<4,000/mm³. Patients were randomly assigned in a 1:1 allocation ratio to the rifaximin group (n=100), which received rifaximin 550 mg orally twice daily for 4 weeks, or the placebo group (n=100). At baseline, all patients underwent clinical evaluation, complete blood count, liver and kidney function tests, and abdominal ultrasonography. A follow-up complete blood count was performed after 4 weeks. Patients were followed weekly in the outpatient hepatology clinic to assess treatment compliance, adverse effects, and cirrhosis-related complications